The Utility of Poly(gamma-glutamic acid) Nanoparticles as Antigen Delivery Carriers in Dendritic Cell-Based Cancer Immunotherapy

摘要

Cytotoxic T-lymphocytes (CTLs) specific for tumor-associated antigens (TAAs) act in the immune surveillance system as major effector cells to eliminate malignant cells Immunization with TAA-loaded dendritic cells (DCs) has great potential for treating cancer, because DCs are potent antigen-presenting cells capable of inducing antigen-specific CTLs by the primary activation of naive T-lymphocytes The establishment of a non-cyto-toxic and efficient antigen delivery method is required to Improve the efficacy of DC-based cancer immunotherapy We developed biodegradable poly(gamma-glutamic acid) nanoparticles (gamma-PGA NPs) that can efficiently entrap various proteins as antigen delivery carriers gamma-PGA NPs efficiently delivered entrapped antigenic proteins into DCs without cytotoxicity and presented antigens to DCs via major histocompatibility complex class I and II molecules Immunization with TAA-loaded DCs using gamma-PGA NPs inhibited tumor growth by inducing TAA-specific CTLs These findings indicate that gamma-PGA NPs can function as useful antigen delivery carriers in DC-based cancer Immunotherapy